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LBA511 Background: TX05 is being developed as a biosimilar to trastuzumab. We previously reported results of a Phase III study (TX05-03) comparing the efficacy and safety of TX05 to originator trastuzumab (TRA) in patients with HER2+ early breast cancer (EBC). The rate of pathologic complete response for subjects treated with TX05 compared to TRA in the TX05-03 study were within pre-defined equivalence margins, supporting the therapeutic equivalence of TX05 and TRA. This is an extension study to further assess and characterize the safety, immunogenicity, and efficacy of TX05 and TRA as single agents. Methods: TX05-03e was a randomized double-blinded, parallel group Phase III trial with patients enrolled at 82 centers in 10 countries. Adjuvant treatment included single agent trastuzumab (TX05 or TRA) for up to thirteen 3-week cycles. Subjects originally assigned to TX05 in the neoadjuvant phase of treatment received TX05, while subjects randomized to TRA in the neoadjuvant phase were randomized (1:1) to receive either TX05 or TRA. Efficacy endpoints include assessment of disease-free survival and overall survival. DFS is defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) to the documentation of a first failure. OS is defined as the time from randomization in the neoadjuvant study until death from any cause. Safety parameters assessed include treatment emergent adverse events (TEAE) and serious adverse events (SAE), death, clinical laboratory parameters, vital signs, 12-Lead ECG, LVEF and Physical examination. Immunogenicity was also assessed. Results: Of the 338 subjects randomized, 256 received TX05 while 82 received TRA. 81 of the TX05 patients received TRA in the neoadjuvant treatment phase. Demographic and baseline characteristics were well balanced between the three arms (TX05/TX05, TRA/TRA, or TRA/TX05 in neoadjuvant/adjuvant treatment phases). There was one death reported (TRA/TX05 group due to disease progression). DFS events occurred in only 3.4% of the TX05/TX05 group, 6.1% of the TRA/TRA group and 3.7% of the TRA/TX05 group. The number of subjects with any AE was 53.1% in the TX05/TX05, 56.1% in the TRA/TRA group and 37% in the TRA/TX05 groups. Frequency, type and severity of adverse events related to study drug were similar between the three groups and no new safety signals were detected. Conclusions: The rates of DFS, OS, AEs and immunogenicity were comparable in subjects randomized to TX05/TX05, TRA/TRA or TRA/TX05 for neoadjuvant/adjuvant treatment and continue to support the conclusion of biosimilarity of TX05 to the reference product. The change from TRA to TX05 for adjuvant treatment has no detectable impact on safety or treatment outcome. Clinical trial information: NCT04109391.

e21049 Background: Local and international recommendations for anticancer treatment are formed and changed based on the results of clinical trials. A feature of most clinical trials is the strict criteria used to select “safe” patients without severe comorbidities. In real world practice, significant portion of patients do not meet all of these criteria (32%) [ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586241/ ], which raises a significant question about the consistency of treatment results demonstrated in studies with data obtained in routine clinical practice (RCP). The purpose of this work was to compare the results of treatment of patients with unrespectable NSCLC receiving first-line drug therapy in RCP and in the framework of international clinical trials using the method of pseudo-randomization (propency score analysis). Methods: The current analysis included 344 patients with inoperable NSCLC who received first-line drug therapy as part of RCP and 90 patients included in various non-TKI clinical trials irrespectively of IO use 2018-2019.Firstly, a direct comparison of performance indicators was done (progression-free survival) using the Kaplan-Meier method for all patients included in the study.At the second stage, in order to eliminate the influence of the imbalance of prognostic factors, a regression analysis was carried out. To form balanced cohorts, we used the propensity score matching analysis.The propensity to progression was assessed using logistic regression analysis in each individual patient, taking into account the basic clinical characteristics: age, gender, ECOG, histological form, regional lymph nodes, presence of distant metastases (mts), stage of the disease, mts of the lung parenchyma, liver mts, pleural mts, bone lesions, adrenal mts, mts lesions of distant lymph nodes, mts lesions of other areas, mts lesions of the brain, number of metastasis zones, components of the first-line therapy regimen. Patients of both arms treatment were matched in a 1:1 ratio based on their progression propensity score in increments of 0.15.After matching two homogeneous groups of patients were formed: 83 in the RCP group and 84 in the clinical trial therapy group. Results: In a direct comparison of the results of the treatment, progression-free survival in the group of patient who underwent treatment in clinical trials was significantly higher than within the RCP (6.4 months 95% CI 5.9–6.9 vs. 13.3 months 95% CI 8.1–18.5; log rank p < 0.000).propensity score matching analysis showed a significantly longer time to progression in the clinical trials group of 13.3 months, 95% CI 8.3-18.3 versus 6.3 months. 95% CI 4.8-7.7; log rank p < 0.000. Conclusions: Results obtained in clinical trial are substantially better than seen in RCP, this should be taken into consideration when extrapolating new research findings.

e15078 Background: It is known that berberine inhibits oxidative phosphorylation by suppressing respiratory complex I function, but the exact mechanism of this phenomenon has not yet been described. The aim of the study was to evaluate the effect of residues in positions 8 and 13 of berberine molecule on the energy metabolism of HeLa cells. Methods: HeLa cells were seeded in an amount of 2*104 cells per well in a Seahorse XFp Analyzer plate (Agilent, USA) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion, the medium was decanted, and the medium with test substances at a concentration of 5 µM was added. Four variants of the experiment, 3 repetitions each, were set up: 1) control; 2) berberine without modification; 3) modification 1 (M1) with the addition of 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl residue at position 13 and malononitrile residue to position 8; 4) modification 2 (M2) with the addition of dicyanovinyl residue at position 13. After 24 hours the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured on Seahorse XFp Analyzer (Agilent, USA) using a Seahorse XFp Cell Energy Phenotype Test (Agilent, USA), with 2 µM FCCP and 1 µM oligomycin. Results: Incubation with the original berberine resulted in a significant decrease in baseline OCR by 39.3±2.8% (M±SD) compared to control (α = 0.05, df = 4), but the maximum OCR did not change significantly. At the same time, a significant increase in the baseline level of glycolysis was observed proportional to the decrease in the baseline OCR, as can be seen from the increase in ECAR by 32.9±5.3% compared with the control (α = 0.05, df = 4). Berberine M1 modification led to a significant increase in baseline OCR by 49.1±2.1% compared with the control (α = 0.05, df = 4), which was also accompanied by a significant increase in maximum OCR by 22.8±3.8% (α = 0.05, df = 4), while the increase in the baseline level of ECAR by 9.7±4.2% was not significant. The addition of the M2 modification did not significantly change the measured parameters compared to the control. Conclusions: The introduction of a dicyanovinyl residue into the berberine molecule at position 13 abrogated its ability to inhibit cellular respiration, possibly due to disturbing its interaction with the proteins of the respiratory complex I. Introduction of the bicyclic residue 7-nitrobenzo[c][1,2,5]oxadiazol-4- yl at position 13 and a malononitrile residue at position 8 caused an increase in baseline and maximum respiration levels, that means thereby berberine activity reversal. This effect can be associated either with the ability to uncouple oxidative phosphorylation (similar to FCCP) or to enhance the expression of electron transport chain proteins.

e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*104 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.

e15003 Background: Taxanes and platinum compounds are widely used in cervical cancer chemotherapy. In particular, a combination of 75 mg/m2cisplatin and 175 mg/m2 paclitaxel, which suggests a doses ratio of 1:2.3, is recommended as first-line systemic chemotherapy. Although this combination has performed well in clinical practice, little is known about its effect on cervical cancer cell biology in vitro. This study assessed the effect of combined application of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.07 - 73.6 µg/mL paclitaxel. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with paclitaxel demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 μg/ml to 8 μg/ml. The difference between the mean viability values for each concentration between pure cisplatin and its 1:2.3 mixture with paclitaxel was significant at α = 0.05 (df = 14). The decrease in viability is especially dramatic at non-toxic concentrations of cisplatin (0.03 - 0.5 μg/ml) and is about 60% over this concentration range. However, when moving to toxic concentrations of cisplatin (0.5-32 μg/ml), the difference in the viability of HeLa cells between pure cisplatin and its combination with paclitaxel linearly decreases with increasing cisplatin concentration, becoming insignificant in the range of 8-32 µg/ml. However, when comparing the dose-response curves for pure paclitaxel and its combination with cisplatin, we see a significant reduction in cytotoxic activity compared with pure paclitaxel. The difference in cell viability reaches its maximum (45%) at a paclitaxel concentration of 2.3 µg/ml and is significant at α = 0.05 (df = 14). Conclusions: The combined use of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa culture has a greater cytotoxic activity compared to pure cisplatin. However, compared with pure paclitaxel, the effectiveness of its combination with cisplatin is significantly lower, which indicates the antagonism of the two substances.

e17500 Background: Our purpose was to analyze the rates of polymorphic allelic variants of genes of hemostasis system and methionine exchange in patients with female reproductive tumors. Methods: The study included 51 patients with histologically verified gynecologic tumors (group 1), including 28 patients (group 1a) with malignant tumors (cervical cancer (CC) n = 8, ovarian cancer (OC) n = 8, endometrial cancer (EC) n = 8, other cancers n = 4) and 23 patients (group 1b) with benign tumors, and 47 women without tumors (group 2). 12 polymorphic loci were studied by RT-PCR in genomic DNA samples: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889), MTHFR (С677Т, rs 1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Groups 1, 1a and 1b were compared with controls (p1) and among themselves (p2). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except F7 (G10976A) in group 1 (p = 0.03). An alternative allele in the F2 gene was found only in group 2 (1.1%). The frequency of an alternative allele in the F5 gene in group 1 was 2.9%, including 1a – 1.8%, 1b – 4.3%, group 2 – 2.1%; F7 – 16.7%, 14.3%, 19.6% and 17.0%; F13 – 23.5%, 23.2%, 23.9% and 34%; FGB – 26.5%, 25.0, 28.3% and 25.5%; ITGA2 – 53.9% (p1= 0.03, OR = 1.89 (1.07-3.33), 48.2%, 60.9% (p1= 0.01, OR = 5.21 (1.22-5.17) and 38.3%; ITGB3 – 13.7%, 10.7%, 17.4% and 16.0%; PAI-1 – 47.1% (p1= 0.03, OR = 0.53 (0.30-0.93), 46.4%, 47.8% and 62.8%; MTHFR (Т) – 28.4%, 30.4%, 26.1%, 34.0%; MTHFR (С) – 34.3%, 28.6%, 41.3% (p1= 0.04, OR = 2.17 (1.02-4.61) and 24.5%; MTR – 18.6%, 19.6%, 17.4% and 27.7%; MTRR – 63.7%, 71.4%, 54.3% and 62.8%, respectively. TT genotype at the ITGA2-α2 (C807T) locus was more frequent in group 1 than in group 2 (23.5% vs 19.1%, p1= 0.01, OR = 6.54 (2.61-16.40); CT genotype was more frequent in group 1a than in group 2 (67.9% vs 38.3%, p1= 0.004, OR = 3.40 (1.27-9.13), and more frequent in EC than in group 2 (87.5% vs 38.3%, p1= 0.03, OR = 11.28 (1.28-99.40). GG genotype at the MTRR (A66G) locus was more frequent in group 1a than in group 1b (53.6% vs 26.4%, p2= 0.042). 5G5G genotype at the PAI-1 4G(-675)5G locus was more frequent in group 1 than in group 2 (31.4% vs 10.6%, p1= 0.04, OR = 3.84 (1.28-11.53), and more frequent in OC than in group 2 (75% vs 11%, p1= 0.0001, OR = 25.50 (3.96-160.20). AA genotype at the F7 (G10976A) locus was more frequent in CC patients than in group 2 (31.3% vs 17%, p1= 0.03, OR = 15.33 (1.20-195.75). Conclusions: Carriage of the AA genotype at the F7 (G10976A) locus may increase the risk of developing CC, and the CT genotype at the ITGA2-α2 (C807T) locus may increase the risk of EC. On the contrary, the alternative 4G allele at the PAI-1 4G(-675)5G locus was less common in patients with malignant tumors, especially OC, than in the group without cancer.

e17549 Background: The question of the mechanisms of platinum resistance development in advanced ovarian cancer (OC) remains open. The aim of the study was to reveal the relationship between the proliferative activity of OC cells, the disruption of apoptosis processes and the changes in the activity of transporter proteins that provide the efflux of chemotherapy drugs. Methods: Patients with advanced OC (T3-4N0-3M0-1) of postmenopausal age, sensitive (SPtPs, n = 23) and resistant to platinum drugs (RPtPs, n = 17), operated on after 3-6 cycles of neoadjuvant chemotherapy, were retrospectively studied. The parameters of proliferative activity (ki67), apoptosis disturbances (p53), as well as the expression of BCRP and Pgp transporter proteins were evaluated in OC tissue using immunohistochemistry methods. Statistical analysis was performed using the Mann-Whitney and Pearson tests (χ2), as well as the Spearman's rank correlation coefficient (SC). Results: In total, the dominance of the RPtPs over the SPtPs was noted in terms of intensity of the studied indicators (p < 0.05-0.003), the most significant for Pgp expression. At the same time, moderate and high values of these indicators were observed in SPtPs in 42-61% of cases, which reduced the predictive value of the revealed differences. It was of interest that statistically significant correlations between the indicators in SPtPs differed from those in RPtPs. Thus, the following values of the SC were observed in SPtPs: +0.848 (ki67-p53), -0.675 (ki67-BCRP), -0.575 (p53-BCR). In RPtPs, another intensity and/or direction of these relations were noted: +0.521 (ki 67-p53), +0.500 (ki 67-BCRP), +0.705 (p53-BCR). There were no statistically significant relationships between ki67-Pgp expression in SPtPs and RPtPs. The direction and intensity of the studied relationships could indicate changes in cell regulation in primary OC in SPtPs compared to RPtPs. Thus, in SPtPs, they reflected a significant contribution of apoptotic disturbances to the enhancement of OC cell proliferation, which was limited by the negative feedback mechanism via BCRP activity suppression indicated by the presence of an inverse correlation ki67-BCRP. In RPtPs, this mechanism was apparently already lost, which resulted in a change in the direction of the statistical relationship ki67-BCRP from reverse to direct one. Under these conditions, the positive contribution of apoptosis disruption to the proliferative activity of OC cells could obviously be supplemented by a synergistic increase in the activity of the BCRP transporter protein, which removes platinum drugs from OC cells. Conclusions: Patients with advanced OC may develop platinum resistance due to discoordination of proliferation, apoptosis, and regulation of the activity of the BCRP transporter protein.

e15002 Background: Bleomycin is a glycopeptide antibiotic with anticancer properties. Clinical data indicate a relatively low efficacy of bleomycin in mono regimen, which is also accompanied by side effects from high doses. That’s why so it is more often used in relatively low doses in combination with other chemotherapy drugs. In particular, in cervical cancer, bleomycin is used in combination with cisplatin in a dose ratio of 0.8:1. Despite good clinical results, it is not known how the two drugs interact in vitro. The aim of this study was to evaluate the effect of combined application of bleomycin and cisplatin on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO2. After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.012 – 12.8 µg/mL bleomycin. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with bleomycin demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 µg/ml to 8 µg/ml, and pure bleomycin in the range of 0.012 - 12.8 µg/ml. The difference between the mean viability values for each concentration of pure bleomycin or pure cisplatin and their 0.8:1 mixture was significant at α = 0.05 (df = 14). Observed decrease in the viability of HeLa cells in comparison with pure substances is most pronounced in the range of non-toxic concentrations for both substances in mono regimen, namely 0.03 - 0.5 μg/ml for cisplatin, and at concentrations less than 0.125 μg/ml for bleomycin. Here, the increase in the difference between the dose-response curves grows as the concentration of the studied drugs increases. At cisplatin concentrations of 0.5–32 μg/ml, the difference in HeLa cell viability between pure cisplatin and its combination with bleomycin, on the contrary, decreases linearly with increasing cisplatin concentration, becoming insignificant above 16 μg/ml. Conclusions: The combined use of bleomycin and cisplatin on HeLa culture in a dose ratio of 0.8:1 exhibits synergistic properties that are most pronounced in the concentration ranges of both substances that do not have a cytotoxic effect in mono regimen.

e17554 Background: Thrombosis in patients with gynecologic cancers worsens the outcome of antitumor treatment and is one of the leading causes of their death. The kallikrein-kinin system (KKS) is involved in both the regulation of thrombus formation and the development of cancer. The purpose of this study was to analyze characteristics of the KKS components in the blood in patients with endometrial cancer (EM) and ovarian cancer (OC) with and without secondary thrombosis (VTEC). Methods: The study included 39 patients, mean age 58.0±4.2 years: main groups – patients with OC T1c-3cN0M0 (n = 10) or EC T1a-2N0M0 (n = 9) with VTEC; comparison groups - patients with OC (n = 10) or EC (n = 10) without VTEC. EC was represented by adenocarcinomas (G1-G3), OC by serous carcinomas (90%) and clear cell adenocarcinomas (10%). The control group included healthy women of the corresponding age (n = 10). Blood levels of kallikrein 1 (K1), kallikrein 14 (K14), and kininogen (KG) were measured by ELISA after the surgery. Results: EC patients with VTEC showed 1.5 times (p < 0.05) higher blood levels of K1, compared to donors, while other indices were unchanged. EC patients without VTEC had 4 times lower KG levels, compared to donors and EC+VTEC. In OC, regardless of the presence or absence of VTEC, levels of K1 in the blood increased, as well as in women with EC+VTEC, by 1.5 times (p < 0.05) compared with donors, which was combined with a twofold increase in KG in OC+VTEC and a decrease in KG by 1.4 times in OC patients without VTEC. Blood levels of K14 increased only in OC patients without VTEC by an average of 1.9 times (p < 0.05) compared with donors and OC+VTEC. Conclusions: The revealed changes in some KKS components in the blood demonstrate the similarity (K1 increase) and differences (KG increase only in OC) in the pathogenesis of thrombosis associated with gynecologic cancers. The mechanisms of protection against VTEC in the early postoperative period also showed common (KG decrease) and specific features associated with the characteristics of cancer (K14increase only in OC). The development of therapy aimed at correcting the identified disorders will allow an antitumor treatment program for this category of patients with maximum efficiency improving their quality of life and survival.

e15119 Background: With the spread of CTMP in cancer patient management and expansion of molecular-targeted treatment opportunities, resources for quick and efficient molecular profile interpretation are in high demand. Number of public KBs have been introduced. We analysed their utility to compile per patient treatment recommendations. Methods: Analysis was performed across patients, who underwent CTMP. Based on the reported molecular alterations, interpretation and critical evidence evaluation was performed not taking into account the recommendations provided in the original CTMP reports. Therapy recommendations were ranked according to ESCAT. Resistance biomarkers were ranked according to OncoKB V2 level of evidence system. OncoKB, CIViC, CGI, CGA, VICC and MolecularMatch were assessed. KBs were assessed through API or local copy of KB. Results: A total of 222 CTMP reports from 222 patients (35% - NSCLC; 24% - CRC; 8% - pancreas; 7% - breast; 4% - gastric; 22% - other) were analysed. CTMP was performed in Foundation Medicine (82%) or Atlas Oncology Diagnostics (18%). Across 222 patients 932 molecular alterations were identified. A total of 1394 therapy recommendations were compiled associated with 368 molecular alteration across 171 (77%) patients (112 recommendations ESCAT level I; 908 - ESCAT III-IV; 70 - OncoKB R1). Across 181 ESCAT-I/R1 therapy recommendations 172 (95%) were present in at least 1 KB (92% for ESCAT-I recommendations, 100% - R1) with the VICC providing the highest rate of retrieval (80%), followed by OncoKB (78%), MolecularMatch (70%), CIViC - (69%) and CGI (69%). Only 92 (53%) of ESCAT-I/R1 therapy recommendations were present in all KBs. Across 27 patients with ESCAT-I recommendations, at least 1 therapy recommendation was retrieved in any KB for all patients. ESCAT II-IV therapy recommendations were provided for 161 patients and grouped by drug class, resulting in 457 [biomarker]-[drug class] associations. Of them 346 (75%) were present in at least 1 KB with the VICC providing the highest rate of retrieval (69%), followed by CGI (61%), CGA (56%), OncoKB (48%), CIViC (48%) and MolecularMatch (45%). Of 161 patients, for 24 (15%) no recommendations were retrieved in any KB for any biomarker identified. For random 15 (a total of 68 molecular alterations) patients KBs were assessed manually in order to estimate the average time in use. CGI was the most easily accessible (3.2 min per patient in average), following by CGA (5.6 min), OncoKB (7.2 min), CIViC (26.2 min), and VICC (35.9 min). Conclusions: Public KBs provide substantial information on ESCAT-I/R1 biomarkers and decent information on ESCAT II-IV biomarkers, reasoning manual curation. VICC provided the most complete information, though was thorough for manual use. The use of multiple KBs may significantly improve retrieval results, though is time-consuming and results in excess of misleading/outdated recommendations.

e21512 Background: Improved overall survival in patients undergoing metаstasectomy for melanoma have been reported in several retrospective studies before era of modern therapy in melanoma. Rapid progress in BRAF and MEK targeted therapy (TT) and immunotherapy (IT) has led to significant improvements in objective response rates and survival rates in advanced melanoma patients. Unfortunately, part of patients have a resistance to modern therapy in one or more lesions. In 2019 Nelson DW et al published data when surgery followed by modern therapy in 47 matched pairs was associated with higher 5-year melanoma-specific survival (MSS) versus modern therapy alone (58.8% vs. 38.9%, p = 0.049). But data about modern therapy in BRAF + advanced melanoma with metastasectomy during therapy are limited. Methods: We conducted an observational retrospective chart review study and evaluated a subset of patients which underwent surgery (metastasectomy) with V600 BRAF-mutant advanced melanoma, who received therapy in a real-world setting in Russia. Survival analyses were performed using the Kaplan-Meier method, Log-rank, chi-square and Fisher exact tests were used for comparison between groups. Results: The observed population included 382 patients in Russia. The date of the first enrollment after all approvals was 8 October 2018, and the date of the last completed register was 27 April 2019. Among 382 patients, 107 (28%) patients received surgical treatment for advanced melanoma during modern therapy (removal of metastases from the brain, lungs, soft tissues and other organs). Surgery during first line therapy was performed in 60pts (56%), as second – in 25pts (23.4%) and third or higher line in 22pts (20.6%). Comparison of overall survival curves for all patients depending on the surgical treatment showed that the survival in the subgroup of patients with the presence of surgical treatment was higher than among patients who did not undergo metastasectomy: 24-months OS was 76.7 (95%CI, 65.6 – 84.6) and 53.7% (95%CI, 46.4-60.4), p = 0,0027). Conclusions: Our findings suggest that resection of distant metastases associated with improved overall survival despite all limitations in retrospective nature of the study. While modern systemic therapy have improved outcomes in advanced melanoma, metastasectomy remains associated with favorable survival. Surgery have to be a part of multidisciplinary care for patients with advanced melanoma.

e17621 Background: An imbalance of sex hormones in endometrial cancer (EC) towards hyperestrogenism together with progesterone deficiency is considered to stimulate proliferation and suppress endometrial apoptosis. EC with squamous metaplasia is characterized by a more severe clinical course and the lack of an adequate response to standard treatment. The purpose of this study was to analyze the local hormonal profiles of tumors with squamous metaplasia in patients with obesity. Methods: The main group included 20 EC patients with squamous metaplasia, and control group included 35 patients with endometrioid adenocarcinoma: T1-3N0-1M0, mean age 64±3.2 years. Intact endometrial tissues were obtained during surgical treatment of patients with uterine fibroids (n = 20). All patients gave their written informed consent for the study. Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), estrogen receptors ERα and ERβ, progesterone receptor RP4 and androgen receptors RA were measured by ELISA in samples of tumor and peritumoral (PT) tissues. Statistical processing of results was performed using the Statistica 10. Results: Tumor tissues of patients with EC, regardless of the histological structure, showed higher levels of estrogens and androgens and their receptors, compared with the intact endometrium, without significant changes in levels of progesterone and its receptor. In the main group, compared with the control group, E1 levels in tumors were lower by 1.6 times, E2 by 1.3 times (p < 0.05), but T higher by 2.4 times, ERα by 1.7 times, ERβ by 1.5 times (p < 0.05). PT, compared with the intact endometrium, had lower levels of E1 and E2 by 2 times and 1.5 times, P4 by 5.1 times, and T was lower only in PT with squamous metaplasia by 2.8 times. Levels of all steroid hormone receptors in PT were higher, regardless of the histological type of tumors. In PT of the main group, levels of E1 were 1.3 times lower (p < 0.05) than in controls, P4 – by 2.2 times, T – by 2.8 times, RP4 – by 1.7 times and ERβ by 1.8 times (p < 0.05), but ERα was 3.2 times higher. Conclusions: Tumors with squamous metaplasia, compared with endometrioid adenocarcinoma, are characterized by an imbalance of steroid hormones towards the predominance of androgens, and ERα plays a dominant role among estrogen receptors. The tumor probably synthesizes sex steroids independently and also pumps them over from the surrounding area. At the same time, malignant endometrial tumors, regardless of their histological structure, are more saturated with estrogens, androgens and their receptors, compared with the intact endometrium.

9016 Background: Teliso-V is an antibody-drug conjugate composed of a c-Met antibody (ABT-700) and a microtubule inhibitor (monomethyl auristatin E). The phase 2 M14-239 trial (LUMINOSITY, NCT03539536) aims to identify the c-Met OE NSCLC populations best suited to Teliso-V (Stage 1) and expand selected groups for further evaluation of efficacy (Stage 2). In Stage 1, pts were enrolled into cohorts defined by histopathology (non-squamous [NSQ] or squamous [SQ]) and EGFR mutation status (mutant or wild type [WT]); NSQ cohorts were further divided in groups on the basis of c-Met expression (high or intermediate). Updated data from the fourth interim analysis (IA4) are presented. Methods: Pts had locally advanced/metastatic NSCLC, ≤2 prior lines of systemic therapy, ≤1 line of chemotherapy, and tumors that were c-Met OE by central immunohistochemistry (IHC; Ventana; Tucson, AZ). c-Met OE was defined for the NSQ cohort as ≥25% 3+ by IHC (high, ≥50% 3+; intermediate, 25 to

e21120 Background: Various EGFR TKIs and several combinations are the standard of initial treatment for NSCLC with EGFR mutations. For this moment one size fits all approach is used. Due to the limited nature of this subgroup direct prospective survival comparison of various options is time and resource consuming. The main objective of this study was to compare available prospective trials in a network meta-analysis in order to determine the overall survival (OS) advantage. Methods: Using frequentist approach (netmeta R package) we performed a network meta-analysis of prospective randomized trials comparing having platinum doublet or 1G TKI as a control arm and 1G TKI, 2G TKI, 3G TKI, combination of chemotherapy (CT)+1G TKI, combination anti-VEGF/R+1G TKI as investigation arm in pts with EGFRmut NSCLC. Between trials we compared OS and progression free survival (PFS ) for overall population and subgroups by mutation, sex, age, smoking status. Results: 17 trials involved 4671 pts were considered eligible for meta-analysis. Trials investigated various combinations of TKIs in untreated EGFR mutated NSCLC: 8 had chemotherapy (CT) as control arm (ENSURE, EURTAC, IPASS, NEJ002, OPTIMAL CTONG-0802, WJTOG3405, LUX-Lung-3/6) and 9 with 1G TKIs as control arm (JO25567, NEJ026, 14034 H3E-CR-JIMIT, NEJ009, Noronha et. al, LUX-LUNG7, ARCHER1050, SWOGS1403, FLAURA). Compared to 1G TKIs improved OS was observed for combination of 1G TKI and CT (HR 0.64 (0.53– 0.78)), 3G TKIs (HR 0.80 (0.64-1.00)), 2G TKIs (HR 0.83 (0.72-0.96)) (The OS benefit was ranked No.1 for TKI+chemo (P-score – 0.96), No.2 – 3G TKI (P-score – 0.68), No.3 – 2G TKI (P-score – 0.64)) Addition of anti-VEGF/R therapy did not improve OS (HR 0.91 (0.68-1.21) over 1G TKIs alone. Importantly OS advantage remained significant in a subgroup of ex19del only for 2G TKIs (HR 0.71 (0.53-0.96)). No advantage for particular regimen was seen for L858R subgroup. 3G TKIs (HR 0.46 (0.27-0.78)), combinations with CT (HR 0.55 (0.40-0.75)) and anti-angiogenic agents (HR 0.57 (0.37-0.89), improved PFS over 1GTKIs, while 2G TKIs had a tendency for improving (HR 0.78 (0.58-1.06)). Conclusions: Our network meta-analysis showed that compared to initial treatment with 1G TKI monotherapy - 1G combination with CT, monotherapy with 3G and 2G may provide OS advantage. Still for ex19del subgroup OS benefit was significant only for 2G TKI. The availability of multiple first line options force the importance of stratification of patients for particular treatment type.